NO792009L - PROCEDURES TO MAKE THE SURFACE OF THE GLASS NON-THROMBOOG - Google Patents

Description

Method of making the surface au glass non-thrombogenic

The present invention relates to a method for making the surface of glass non-thrombogenic and non-thrombogenic glass objects obtained by the present method.

One of the biggest obstacles to using non-physiological materials in the biomedical field is especially their thrombogenic effect when such materials come into contact with the blood. This applies particularly in cases where glass containers are used to store blood or plasma for use in transfusions.

In such a case, anti-coagulants are added to prevent rapid coagulation of the blood caused by contact with the glass surface. This method is not free from disadvantages and dangers as the anti-coagulants present in the blood or plasma constitute an additional risk factor in the case of repeated or large-scale transfusions, and moreover they seem to limit the storage stability of the blood with time.

As glass is a more or less ideal material in light of its mechanical properties, its non-toxicity, its workability. hot, its low price and transparency, a method which eliminates its thrombogenic nature, thus making it suitable not only for the production of blood or plasma containers, but also for use as a component of artificial prostheses or medical-surgical protection, would obviously constitute a big step forward in the bio-engineering field. Such a method has now been discovered and forms the basis of the present invention.

The present method essentially consists in modifying the surface of glass by chemical grafting of polymer chains which are able to form a complex with, and thus stably fix, eparin. In this way, a stable layer of heparin is formed on the glass surfaces, which prevents coagulation of the blood that comes into contact with the treated surfaces, but without introducing into the blood foreign compounds that could change its properties. Moreover, the chemical modification of the surface of the glass according to the present invention in no way changes its mechanical properties, or any of the properties which, as already mentioned, make its use very desirable in the medical field.

Glass objects can be produced by the usual shaping methods before being subjected to the eparinization treatment, and can therefore be shaped in any desired way.

The new method also does not require special types of glass, but can be used on any type of glass provided it contains silicon.

In particular, it can be used on objects made of pure silicon oxide, such as quartz glass and the like.

The new method essentially consists in chemical bonding, to the glass surfaces, of polyamide-amino polymers which are able to form stable complexes with heparin, by means of molecular bridges over the aforementioned grafting surfaces.

The polyamide-amino polymers used in the new method are partly known polymers and partly new polymers.

They are all produced by polyaddition of disecondary diamines

or primary monoamines to bis-acrylamides, and can be expressed by the general formula:

where R and R^ are linear or branched alkyl groups containing 1-6 carbon atoms, or together with the two nitrogen atoms to which they are attached, form a heterocyclic ring, optionally substituted with alkyl groups with 1-3 carbon atoms;

A is an amino group with the formula:

where R' and R" are alkyl groups with 1-6 carbon atoms, or together with the nitrogen atoms to which they are bound, form a hetero-

cyclic ring which is either simple or is substituted with alkyl groups of 1-3 carbon atoms, or

where R"* is a linear or branched alkyl group with 1-6 carbon atoms, optionally substituted with amino-, carboxyl-, alkoxy-silane or amino-alkoxy-silane groups.

The polymers comprising monomeric purity are derived from primary monoamines with the formula P^N-R"' where R"<*> is an alkyl-alkoxy-silane or an amino-alkoxy-silane group, are new polymers.

The others are known polymers (see F. Danusso, P. Ferruti "Polymer" volume 11, pages 88-113 (1970)).

Eparin is well known as a mucopolysaccharide containing equimolar amounts of glucuronic acid and glucosamine, and is characterized by a large number of sulfonic acid and aminosulfonic acid groups:

The large number of sulfonic acid groups gives it the character of a polyanion with a high negative charge. This explains its ability to form stable complexes with the aforementioned polyamide-amino polymers (M. Marchisio, P. Ferruti et al. European Journal of Pharmacology 12 (1970), 236-242).

The main purpose of the present method is to create chemically stable molecular bridges between the glass surfaces and the polyamide-amino polymers, which allow surface heparinization of glass objects, which can be achieved by various alternative methods as described below, all of which are equivalent with regard to the results obtained. 1) The glass surface is, preferably after treatment with strongly acidic solutions such as aqua regia, concentrated hydrochloric acid, concentrated sulfuric acid or concentrated nitric acid, treated hot with a chloridizing agent such as thionyl chloride, PCl^, POCl^, sulfuryl chloride or the like.

In this way, chloridization of the glass surface is achieved by replacing the hydroxyls bound to the silicon with chlorine. The objects are then treated again hot with a polyalcohol which reacts with the surface atoms of Cl, so that mono- or poly-hydroxylated hydrocarbon chains are grafted onto the surface. Polyalcohols suitable for this step of the method are glycols with 2-11 carbon atoms, glycerol, pentaerythritol, mannitol or the like.

It is then finally treated with an excess of acid chlorides such as di- or polycarboxylic acids, di- or polysulfonic acids, which react with the hydroxyl groups in the polyhydroxylated chains to form ester bonds, and introduce chains with -C0C1.or

-SC^Cl end groups which can further react with a polyamide amine with amino end groups, binding it stably by means of covalent bonds of the amide type. The temperature, the solvent and the reaction time used in each of the method steps obviously depend on the particular reagent (chloridizing agent, polyalcohol, acid chloride, polyamido-amine) that is chosen, and is characteristic of the individual products. The polyaraid amine is prepared by reacting, in solution, mixtures of monomers selected from the following groups: I - disecondary diamines of the formula

where R * and R" are alkyl groups with 1-6 carbon atoms, or which, together with the nitrogen atoms to which they are attached, form a heterocyclic ring that is either simple or substituted with one or two alkyl groups with 1-3 carbon atoms, - primary monoamines with the formula I-^N-R"' where.R"<*>is a linear or branched alkyl group with .1 - 3' carbon atoms, optionally substituted with amino-, carboxyl-, alkyl-alkoxy-silane or amino-alkoxy-silane groups.

11 - bis-acrylamides with the formula:

where R, R^ and are linear or branched alkyl groups with 1-6 carbon atoms, or together with the two nitrogen atoms to which they are attached, form a heterocyclic ring which is single or substituted with one or two alkyl groups with 1-3' carbon atoms.

As the polyaddition is practically quantitative, it is for

to obtain polymers with terminal amino groups it is necessary to prepare monomer mixtures containing a molar excess of amine. Preferred solvents are water. or lower alcohols, and protic solutions agents in their generality. Temperatures of 15° to 60°C are used, with times varying from a few hours to a few days depending on the mixture to be polymerized and especially on the amine used.

The method according to this embodiment is represented e.g. of the following series of reactions in which specific reagents are indicated for clarity:

2) The glass surface is, preferably after treatment with strongly acidic solutions, treated at the ambient temperature with a solution of tu-aminoalkyl-trialkoxysilane with the formula

. (RO)3Si-(CH2)n NH2or with the formula (RO)Si(CH2)n-NH(CH2)n-NH2 where R is alkyl with 1-3 carbon atoms, and n is 1-3«

After 2 to 6 hours, which varies depending on the silane compound used, the excess reagent is removed, and the glass surfaces on which the aminosilane groups have been grafted are treated with an acid chloride in solution, selected from the group of acid chlorides as indicated in the previous section 1) .

The chains grafted onto the glass thus receive terminal acid chloride groups, which, during the subsequent heat treatment with a solution of polyamide amine comprising terminal amino groups as indicated above, react with the aforementioned amino groups and bind the polymer chains stably by amide bonds.

The chemical grafting procedure for the glass in this embodiment can be illustrated by the following series of reactions, in which specific reagents are used for clarity:

3) The glass surface is, preferably after treatment with a strongly acidic solution, treated at the ambient temperature with the solution of an aminosilane compound as indicated in the previous section 2). After a few hours of reaction, the excess reagent is removed, and the chemically modified glass surface comprising amino end groups is treated with a polyamide amine comprising activated vinyl end groups.

Such a polyamide-amine is prepared exactly as described under section 1), but this time using a molar excess of bis-acrylamide so that these monomers form the end groups and thus provide the activated vinyl end groups.

A series of reactions illustrating the method of the present embodiment is provided below using specific reagents for convenience:

4) A polyamide-amine is prepared of the type described at the beginning of the description, suitable for stably fixing heparin and which consists x at least partially of amino groups of the type

where R"<*> is alkyl

with 1-3 carbon atoms, substituted with an alkyl- alkoxysilane group or an aminoalkyl- alkoxysilane group as indicated above.

The polymerization is carried out in a solution, preferably of protic solvents, using ionomer mixtures consisting of 50 mol% bis-acrylamides and 50 mol% amines as indicated, consisting in whole or in part of primary amines containing alkoxysilane groups.

It has been shown that the amino-silane compound reacts in the said mixture like the other primary amines indicated above, pg giving polyaddition products with the bis-acrylamides by substituting a hydrogen atom on the vinyl groups of the bis-acrylamides.

The working conditions are a temperature of 15° to 6o°C and a time of a few hours.

These new polymers obtained in this way react with the glass surface, preferably pre-treated with strong acids, and are stably grafted onto it by means of Si-O bridges.

The reaction that characterizes this embodiment of the chemical modification process for the glass surface can be schematically stated as follows:

The grafting reaction takes place at a temperature of from 15°

to 50°C, using a solution of polymer, preferably in a protic solvent such as water or alcohol.

As stated at the outset, the surface radiodification processes which concern only Si-OH groups can be carried out with articles of any type of glass, especially articles of ordinary glass.

Glass objects that have been subjected to any of the treatments described above are then subjected to heparinization treatment by immersion in dilute heparin solutions for a few hours... Preferably a solution consisting of 2 - 3% heparin (sodium salt) in a 1:1 mixture of water is used and ethyl alcohol, containing 2-4% acetic acid. The optimal contact time is approx. 5 hours.

After this time, the glass surface is coated with a layer of chemically bound heparin and is therefore stably non-thrombogenic.

The subsequent chemical modification steps for glass according to the present invention can be followed by means of ESCA spectroscopy, which is particularly a surface analysis method which is sensitive to the outermost layers of solid substances, at a depth which does not exceed 20 - 30 Angstroms.

In order to elucidate the present method in more detail and to make it more easily producible in its various alternative embodiments, some examples are given in the following which in no way limit the scope of the invention as stated in the claims.

Example 1

20 test pieces of ordinary glass with a size of approx.

2 cm x 1 cm x 0.05 cm are immersed in aqua regia for 15 minutes, then washed several times with distilled water and dried at kO°C and 0.1 mm Hg.

An ESCA analysis of these test pieces clearly shows peaks characteristic of the constituents of the glass: Si (1330 and 1382eV); O (952 eV) ; Ca (about 1135 eV); Na (Zfl2 and 985 eV) .

These test pieces are immersed in 50 ml of thionyl chloride, boiled under reflux for 2 hours and then taken out of the thionyl chloride, dried and washed several times with chloroform and anhydrous ether.

ESCA analysis shows at this point that Cl is introduced on the glass surface, the peak at 1285 eV appears clearly, plus a trace of S which gives a weak peak at 13-16 eV.

After analysis, the test pieces are immersed in 10 ml of anhydrous glycerol dissolved in 50 ml of chloroform and heated for 2 hours. They are then washed with chloroform, dried under vacuum and immersed in a solution containing 10% isophthaloyl chloride in anhydrous chloroform and a few drops of pyridine. The solution is heated to 70°C for a further 2 hours. The test pieces are then taken out and washed for a longer time with chloroform.

A polyamide amine was prepared separately by copolymerizing 1,4-bisacryloylpiperazine and N,N<*->dimethylethylenediamine in aqueous solution in an amine:amide mol ore ratio of 1:0.985. After stirring, the homogeneous aqueous solution was left at 18-20°C for 2 days in an inert gas atmosphere. The viscous solution was then poured into acetone, and the gummy precipitate was separated, washed with acetone and placed under acetone for 1-3 hours at room temperature.

The polymer is transferred in this way to a crystalline powder which is collected by filtration and dried.

The glass test pieces from the reaction with isophthaloyl chloride are immersed in a 10% solution of polyamide amine in anhydrous chloroform, and the entire mixture is heated to 70°C for 2 hours. After cooling, the test pieces are taken out, washed with chloroform, water and ethyl alcohol and dried under vacuum.

An ESCA analysis carried out at this time clearly shows the following surface modifications: a) the silicon peaks are halved in intensity, which shows the presence of a material layer covering the surface, b) a nitrogen peak clearly appears at approx. 1085 eV, indicating surface grafting of the polyamide amine.

Finally, the test pieces are immersed for 6 hours in a 2% solution of heparin in a water:ethyl alcohol:acetic acid mixture in the ratio 50:50:3• The test pieces are then washed with water and alcohol and dried in an oven at 40°C and 0.1 mm Hg.

An ESCA analysis gives the following results:

a) the intensity of the silicon peak is further reduced, indicating a further coverage of the glass surface; b) the nitrogen peak has been strengthened and has changed shape, which indicates the fact that the polyamide-amine nitrogen peak has entered

addition to the heparin nitrogen peak; a strong S-peak has appeared at 1316 eV, which is characteristic of heparin.

The sequence of data obtained by ESCA analysis shows without a doubt the chemical binding of the polyamide-amine to the glass surface by means of the previously formed molecular bridges, and then the fixation of the heparin, chemically bound to the polyamide-amine chains.

The procedure described above was repeated in an essentially identical manner using the following groups of reagents: - SOC12; ethylene glycol; succinic chloride; polyamide-amine obtained by copolymerization of a mixture of N,N<*->diisopropylethylenediamine and 1,4-bisacryloylpiperazine in a molar ratio of 1:0.985 - PCl^; butylene glycol; isophthaloyl chloride, polyamide-amine obtained by copolymerization of a mixture of ethylamine and 1,4-bis-acryloylmethylpiperazine in a molar ratio of 1:0.985, - SOC12» pentaerythritol; gl utars<y>rechloride; polyamide-amine obtained by copolymerization of a mixture of methylamine and a bis-acrylamide with the formula:

in a molar ratio of 1:0.950.

Example 2

20 test pieces of ordinary glass like those used in the previous example were immersed in concentrated hydrochloric acid for 20 minutes, then washed several times with distilled water and

o

dried at 40 C and 0.1 mm Hg. The test pieces were immersed in 50 ml of a 10% solution of Y~arninoProPyl-triethoxysilane in methanol and thus left at room temperature for 6 hours. They were then washed with methanol, dried at 20°C and 0.1 mm Hg and was treated for 3 hours under reflux with 50 ml of a 10% solution of isophthaloyl chloride in anhydrous chloroform. The pieces were then taken out, washed with anhydrous ether and treated for 6 hours under reflux with 50 ml of a 10% solution of polyamide-amine in chloroform The polyamide-amine used was obtained by copolymerizing mixtures of 1,4-bis-acryloylpiperazine (48 mol%), as-N,N-dimethylenediamine (26 mol%) and glycine (26 mol %).

The mixture was kept for 5 hours at room temperature, after which the polymer was filtered off and redissolved in chloroform.

The glass test pieces which had reacted with the polyamide amine were taken out, washed with chloroform, water and ethyl alcohol, and subjected to heparinization by treatment for 6 hours with a 2% solution of heparin in a water:ethyl alcohol:acetic acid mixture in the ratio of 50 :50:3-They were finally washed and dried.

The successive surface modifications of the glass were followed by ESCA analysis which gave the following characteristic data: 1) Reaction with Y-aminopropyl-triethoxysilane: Si peaks (1330 and 1382 eV), the 0 peak ( 952 eV) and the N peak (1085 eV) were obtained.

2) Reaction with isophthaloyl chloride:

The Cl peak appeared at 1285 eV, while the N peak became weaker.

3) Reaction with polyamide amine:

The Cl peak became much weaker, while the N peak was again strengthened and changed shape.

4) Reaction with heparin:

The N peak increased further and was modified in shape, and a strong S peak appeared at 1316 eV.

The analysis data confirm without a doubt that an effective chemical modification takes place on the glass surface, and that a layer of chemically bound heparin is formed on the glass.

The above-described procedure was repeated in an essentially identical manner with the following groups of reactants: -U)-aminobutyl-trimethoxysilane; isophthaloyl chloride; polyamide-amine obtained by mixing a bis-acrylamide with the formula

a diamine with the formula

(51 mol%)

methoxysilane with the formula:

(CH 3 O) 3 Si-CH 2 CH 2 CH 2 -NH-CH 2 CH 2 NH 2 ; adipic acid chloridej polyamide-amine obtained from a mixture of bis-acryloylpiperazin (49 mol%) and as-N,N-dimethylethylenediamine (51 mol%)

Example 3

20 glass test pieces of the same dimensions as indicated above are treated with γ-aminopropyl-triethoxysilane exactly as indicated in example 2. After washing the test pieces, which had γ-aminopropyl silane groups on the surface, they are treated with 50 ral of a 10%-ig solution of 1:1 by volume of water:ethyl alcohol, of a polyamide amine obtained by polyaddition of N,N•-dimethylethylenediamine to 1,4-bis-acryloylpiperazine in a molar ratio of 0.98 to 1.

Such a polyamide amine has vinyl end groups.

They are left undisturbed for 5 days at room temperature, then washed with water and ethyl alcohol and heparinized exactly as indicated in the previous examples.

An ESCA analysis of the final product gives characteristic peaks analogous to those found in the final product in the previous examples, and undoubtedly shows surface grafting of the polyamide amine and chemical binding of the heparin.

The described procedure was repeated in an essentially identical manner using the following sets of reagents;

- Y~amiriopropyl~~t rirnethoxysilane; polyamide-amine obtained by polyaddition of 1,4-bis-acryloyl-piperazine (52 mol%), 2,3-trans-piperazine-dicarboxylic acid (24 mol%), as-N,N-dimethylethylenediamine (24 mol% ). - n-aminobutyl-triethoxysilane; polyamide-amine obtained by polyaddition of 1,4-bis-acryloyl-methylpiperazine (51 mol%) and isopropyl-amine (49 mol%) -Y~amiriopropyl-trimethoxysilane; polyamide-amine obtained by polyaddition of 1,4-bis-acryloyl-piperazine (51 mol%), and n-butyl-amine (49 mol%)

- ethoxysilane with the formula:

(C2H^O)3Si-CH2CH2CH2-NH-CH2CH2-NH2; polyamide-amine obtained by polyaddition of 1,4-bis-acryloyl-piperazine (51 mol%) and ethylamine (49 mo.1%).

Example 4

A mixture of 0.1 mol of 1,4-bis-acryloyl-piperazine (prepared according to Danusso, Ferruti and Ferroni, Chimica e Industria 49, 271 (1967)), 0.095 mol of N.N'-dimethylethylenediamine and 0.005 mol of Y -aminopropyl-triethoxysilane in 200 ml of methanol is allowed to stand at room temperature for 2 days.

The highly viscous reaction mixture is then poured into 2 1 ether, the solid product is separated by decantation, washed with ether and dried at 20°C and 0.1 mm Hg. Yield is 96%. The elementary analysis corresponds to the theoretical.

20 glass test pieces such as those used in the preceding examples are treated with concentrated nitric acid and washed with water, and placed for 24 hours in contact with a 5% solution in methanol of the polyamide amine obtained as described above. The glass test pieces are then separated, washed with methanol and ethyl alcohol and heparinized exactly as described in the previous examples. ,

An ESCA analysis of the final product shows the characteristic peaks for nitrogen and sulfur, similar to those found in the final product in the preceding examples, thus showing a similar chemical modification and heparinization of the glass surface.

The described procedure was repeated in an essentially identical manner using the following amide-aminosilane polymers: - 1,4-bis-acryloyl-piperazine 1 mol; methylamine 0.95 mol;

Y-aminopropyl-trimethoxysilane 0.05 mol

- 1,4-bis-acryloyl-piperazine 1 mol; as-N,N<*->dimethylethylenediamine 0.95 mol; Y-arairioProPyxriethoxysilane 0.05 mol

- bis-acrylamide with the formula

ethoxysilane with the formula: - 1,4-bis-acryloyl-piperazine 1 mol; n-propylamine 0.5 mol;

Y-aminopropyl-triethoxysilane 0.5 mol.

Example 5

IO glass test tubes 1 x 10 cm were treated as described in example 1„

After washing and drying, they were filled with blood.

After 1 hour, the blood showed no traces of coagulation, while in untreated glass test tubes used for comparison, the blood was completely coagulated after approx. 10^ minutes.

The same experiment was repeated using groups of 10 glass test tubes 1 x 10 cm, treated by the method according to respectively example 2, example 3 and example 4. In no case did the blood show any traces of coagulation after 1 hour.

Example 6

6 glass tubes off. length 2 cm, with an outer diameter of 1 cm and an inner diameter of 0.8 cm was treated exactly as described in example 1 and then introduced into the lesser vena cava of experimental dogs by the method of V. L. Gott and A. Furuse (FederationProceedings 30, 167-9 (1971)).

After 2 hours the animals were euthanized. In none of the 6 tubes was there the slightest trace of thrombosis. Untreated glass tubes that had been used in a similar way in the same experiment were completely occluded within approx. 15 minutes.

The same experiment was repeated by the same method, each time using 6 dogs, to test glass tubes treated according to the respective example 2, example 3 and example Zf. After 2 hours, the tubes showed no trace of thrombosis in any case.

Claims (12)

1. Process for making the surface of glass non-thrombogenic, characterized in that the surface of the glass is modified by chemical grafting, by means of molecular bridges, with polyamide-amine chains which are able to form a complex with, and therefore stably binds heparin, as the glass surface modified chemically in this way is then treated with a heparin solution. 2, Method according to claim 1, characterized in that the polyamide-amine chains grafted by means of molecular bridges have the following repeating units: where R and R^ are linear or branched alkyl groups of 1-6 carbon atoms, or form together with the two nitrogen atoms to which they are attached, a heterocyclic ring which is either single or substituted with alkyl groups of 1-3 carbon atoms; A is an amino group selected from the group consisting of groups with the formula where R <*> and R" are alkyl with 1 - 6 carbon atoms, or they form, together with the nitrogen atoms to which they are attached, a heterocyclic ring which is either unsubstituted or substituted with alkyl groups of 1-3 carbon atoms, and of groups with the formula where R"* is a linear or branched alkyl group with 1-6 carbon atoms, optionally substituted with an amino-, carboxyl-, alkyloxysilane or aminoalkylsilane group, r . 3. Method according to claim 1 or 2, characterized in that the molecular bridges between the glass surface and the polyamide-amine chains are formed by the following reaction sequence: treatment of the glass surface with a strong chlorinating agent; reaction with a polyhydroxylated compound; reaction with the chloride of a polyvalent acid; reaction with a polyamide amine with amino end groups. 4. Method according to claim 3, characterized in that S0C12, PCI,-, POCl^ or SO2 C12 are used as strong chlorinating agents; that a glycol with 2-11 carbon atoms, glycerol, pentaerythritol or mannitol is used as the polyhydroxylated compound; and as the chloride of the polyhydric acid, a chloride of aliphatic or aromatic bicarboxylic, polycarboxylic, bisulfonic or polysulfonic acids is used. 5. Method according to claim 1 or 2, characterized in that the molecular bridges between the glass surface and the polyamide-amine chains are formed by the following sequence of reactions: reaction with a iu-aminoalkyl-alkyloxysyl compound; reaction with the chloride ay a polyhydric acid; reaction with a polyamide amine with amino end groups. 6. Method according to claim 5, characterized in that the u>-aminoalkyl-alkoxys.ilan compound has the general formula (RO) ^Si-(CH2 ) ^-NHR.^ where R is alkyl with 1-3 carbon atoms, n is 2, 3 or 4» R-^ is hydrogen or an alkylamino chain of .1-3 carbon atoms; and the chloride of the polyhydric acid is selected from chlorides of aliphatic and aromatic bicarboxylic, polycarboxylic, bisulfonic and polysulfonic acids. 7. Method according to claim 1 or 2, characterized in that the molecular bridges between the glass surfaces and the polyamide-amine chains are formed by reaction with an alkoxysilane compound of the formula (RO)^ Si-(CH2 )n -NHR^ where R is alkyl with 1- 3 carbon atoms, n is 2, 3 or 4} R-^ is hydrogen or alkylamino with .1-3 carbon atoms, and subsequent reaction with a polyamide-amine with vinyl end groups. 8. Method according to claim 1 or 2, in characterized by the fact that the molecular bridges between glasses the surface and the polyamide-amine chains are formed by reacting■ the glass with polyamide-amines with monomer units of the formula -N- where R" <*> I is alkyl of 1-6 carbon atoms substituted with alkyloxysilane or aminoalkyl-alkyloxysilane groups which are capable of reacting directly with the surface hydroxyl groups of the glass. 9. Method according to claims 1-8, characterized in that the treatment with heparin is carried out by immersion in a solution containing 2-3% heparin, in a 1:1 (by volume) of water:ethyl alcohol mixture containing 2-4% acetic acid, at room temperature for a few hours. 10. Glass objects which are non-thrombogenic on the surface, characterized in that they have a surface layer of heparin which forms a stable complex with polyamide-amine chains chemically grafted onto the glass surface by means of molecular bridges. 11. Polyamide-amine polymers that can be chemically grafted onto glass surfaces by side chains that form molecular bridges and that are capable of forming stable complexes with heparin, characterized in that they have the formula: where R and R^ are linear or branched alkyl groups with 1-6 carbon atoms, or together with the two nitrogen atoms to which they are attached, form a heterocyclic ring which is optionally substituted with alkyl groups with .1-3 carbon atoms, and A are amino groups which is made up in whole or in part of groups with the formula where R" <*> is alkyl with 1-6 carbon atoms, substi tuated with alkoxysilane groups with the formula (ROj^ Si- or (RO)2Si" (CH2 )n~ NH"" where R is alkyl with 1-6 carbon atoms, and n is 1, 2 or 3. 12. Polyamide-amine polymers according to claim 11, characterized in that the amino groups A, which are not amino-alkoxysilane units, are selected from the group consisting of amino groups with the formula where R<*> and R" are alkyl groups with 1-6 carbon atoms, or together with the nitrogen atoms to which they are attached, form a heterocyclic ring that is either unsubstituted or substituted with alkyl groups of 1-3 carbons atoms, and amino groups with the formula where R"' is a linear or branched alkyl group with 1-6 carbon atoms, optionally sub substituted with amino or carboxyl groups.